Interactions of positively identified human natural killer (NK) cells with appropriate target cells have been studied in serial thin sections with the electron microscope. These studies have been extended to human effectors of ADCC rat NK cells and rat tumor cells with NK and ADCC activities. These cells have been examined (1) under non-activated conditions, (2) at various times during killing of targets and/or (3) under conditions mimicking signals that activate them to kill (adherence to antigen-antibody complexes or activation by lectins). Several murine cytotoxic T cell clones are also being studied and compared with non-cytotoxic clones. All cytotoxic lymphocytes studied thus far contain membrane bound granules, although the granules differ in details of morphology from one species to another. In all cases, the granule contents are secreted by exocytosis under conditions which activate the effectors to kill. The material secreted by all effector types is heterogeneous and has as a major component membraneous structures which often bear ring-shaped profiles on their surfaces. Studies are in progress to identify the granule contents in situ by light and EM immunocytochemistry, and by isolation and characterization by biochemical techniques.